Orion-Yhtyma Oy

Pekka J Kairisalo

Erkki J Honkanen

Aino K Pippuri

Jarmo J Pystynen

Reijo J Backstrom

Erkki A Nissinen

Pentti Pohto

Inge-Britt Y Linden

Kalevi E Heinola

Seppo K Kaakkola

Pekka I Mannisto

Esko Veikko Marttila

Martti Lauri Marvola

Jaakko A Uotila

Sirpa A Tuomi

Heinrich Thaler

Pekka T Mannisto

Maija K Koivisto

Anitta H Jarvinen

Petri J Hukka

A compound according to formula 1 ##STR1## wherein R.sub.1 and R.sub.2 independently represent hydrogen, carbamoyl which is substituted by an alkyl of 1 to 4 carbon atoms, alkylcarbonyl of 2 to 5 carbon atoms or phenyl carbonyl, X represents halogen nitro or cyano and R.sub.3 represents ##STR2## wherein R.sub.4 represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R.sub.5 represents carbamoyl which is unsubstituted or substituted with alkyl of 1 to 8 carbon atoms or which is substituted with hydroxyalkyl of 1 to 8 carbon atoms or pharmaceutically acceptable esters and salts thereof, and a pharmaceutically acceptable carrier therefor, as well as pharmaceutical compositions containing said compounds as COMT inhibitors.

Pharmacologically active catechol derivatives

Catechol compounds of formula I ##STR1## where R.sub.1, R.sub.2, R.sub.3 and X are as described herein are effective Catechol-O-methyltransferase inhibitors.

Pharmacologically active compounds, methods for the preparation thereof

An improved process for the preparation of fluoxetine. The invention is concerned with an improved process for the preparation of the antidepressant, fluoxetine hydrochloride, or N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine hydrochloride, by simultaneous debenzylation and catalytic hydrogenation of 2-benzoyl-1-(N-benzyl-N-methyl)ethylamine base with the aid of Pd/C, Pt/C or Pd-Pt/C at a hydrogen pressure of 5 bar at 50.degree. C. with ethyl acetate as a solvent to obtain 1-phenyl-3-(N-methylamino)-propan-1-ol. This compound is then selectively etherified with 1-chloro-4-trifluoromethylbenzene in N-methylpyrrolidone at 80.degree. C. in the presence of potassium t-butoxide to form N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine, or fluoxetine base, which is transformed in a known manner to fluoxetine hydrochloride, or N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine hydrochloride. The yield of fluoxetine hydrochloride is 85-87% of the theoretical.

Process for the preparation of fluoxetine

The invention concerns a method for the treatment of Parkinson's Disease. The method comprises administering a catechol-O-methyl-transferase inhibiting amount of a compound having the formula I ##STR1## wherein R.sub.1 and R.sub.2 independently represent hydrogen, alkylcarbamoyl of 2 to 5 carbon atoms or alkylcarbonyl of 2 to 5 carbon atoms, X represents nitro or cyano and R.sub.3 represents ##STR2## wherein R.sub.4 represents cyano or alkylcarbonyl of 2 to 5 carbon atoms and R.sub.5 represents cyano; alkylcarbonyl of 2 to 5 carbon atoms; or carbamoyl which is unsubstituted or substituted with alkyl of 1 to 8 carbon atoms, or hydroxyalkyl of 1 to 8 carbon atoms or pharmaceutically acceptable salts or esters thereof; and a sufficient amount of levodopa to treat Parkinson's Disease. A peripheral decarboxylase inhibitor such as carbidopa or benzerazide is also preferably administered.

Method of treating Parkinson's Disease using pentanedione derivatives

Pharmacologically active catechol derivatives of formula I ##STR1## wherein R.sub.1 and R.sub.2 independently comprise hydrogen, alkyl, acyl, optionally substituted aroyl, lower alkylsulfonyl or alkylcabamoyl or taken together form a lower alkylidene or cycloalkylidene, X comprises an electronegative substituent such as halogen, nitro, cyano, lower alkylsulfonyl, sulfonamido, aldehyde, caboxyl or trifluoromethyl and R.sub.3 comprises hydrogen, halogen, hydroxy alkyl, amino, nitro, cyano, trifluoromethyl, lower alkylsulfonyl, sulfonamide, aldehyde, alkyl carbonyl, aralkylidene carbonyl or carboxyl or a group selected from ##STR2## wherein R.sub.4 comprises hydrogen, alkyl, cyano, carboxyl or acyl and R.sub.5 comprises hydrogen, cyano, carboxyl, alkoxycarbonyl, carboxyalkenyl, nitro, acyl, optionally substituted aroyl or heteroaroyl, hydroxyalkyl or carboxyalkyl or R.sub.4 and R.sub.5 together form a five to seven membered substituted cycloalkanone ring;

The invention relates to a new antibiotic compound, acetyl erythromycin stearate having formula I ##STR1## The compound according to the invention is absorbed readily from the alimentary tract. Gastric acid does not convert the compound according to the invention to an uneffective form as is the case with some other erythromycin antibiotics. Absorbing is good also when the patient eats when taking the new medicine. The compound according to the invention is prepared by reacting erythromycin base with acetyl halide in an organic solvent in the presence of an acid acceptor. The stearate salt is prepared from the obtained ester without in between isolating the ester.

Acetyl erythromycin stearate, and compositions containing it

An improved method is disclosed for producing antihypertensively active 6,7-dimethoxy-4-amino-2-[4-(2-furoyl)-1-piperazinyl] quinazoline hydrochloride, viz prazosine hydrochloride, by reacting methyl-N-(3,4-dimethoxy-6-cyano-phenyl)-[4-(2-furoyl)-1-piperazinyl]thiofo rmamidate with a large excess of ammonium chloride.

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Helsinki, Finland

Pekka J Kairisalo